Therapeutic effect of Thymoquinone on behavioural response to UCMS and neuroinflammation in hippocampus and amygdala in BALB/c mice model

Author(s):  
Sadia Nazir ◽  
Rai Khalid Farooq ◽  
Sadia Nasir ◽  
Rumeza Hanif ◽  
Aneela Javed
2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S155-S155
Author(s):  
R Golan-Gerstl ◽  
N Koroukhov ◽  
Y Elbaum Shiff ◽  
I Shilo ◽  
S Reif

Abstract Background Inflammatory bowel disease (IBD) is a complex disorder that results from a dysregulated immune response in the gut. Emerging therapy for IBD treatment is mainly focused on regulation of the immune response. Exosomes are nanovesicle packing different molecules such as miRNAs that transfer their cargo to recipient cells. We and others found that mammalian milk contain high concentration of exosomes (milk-derived exosomes, MDE) carrying beneficial miRNAs such as miRNA-148. Furthermore, MDE are taken up by different cell type such as intestinal epithelial cells, modify target gene expression, promote proliferation and differentiation of colon epithelial cells. The aim of this study is to explore the therapeutic effect of MDE on colitis. Methods We used gavage administration of MDE labelled with DiR dye to track their localisation patterns in vivo. The therapeutic effect of MDE on colitis was study in mice model of SDS induced colitis, colon length, histopathological scoring grade, cytokine expression, stool consistency and miRNA expression were analysed. Results Imaging of mouse that have receive labelled MDE revealed an accumulation of fluorescent signal in the intestine. Moreover, fluorescent signal in the intestine and liver is time dependent. MDE reduced the histopathological scoring grade from 5.83 ± 1.47 to 0.6 ± 0.6, p < 0.05. The length of the colon of MDE-treated animals was 7.9 ± 0.19 in comparison to 6.92 ± 0.3 p < 0.05 of the untreated. The weight loss as a result of the colitis was reverted in MDE-treated mice. Likewise, MDE treatment reduced IL-6, TNF-α and caveolin expression from 3.83 to 0.78, 1.59 to 0.86 and 3.52 to 1.1, respectively. Highly expressed miRNAs (miRNA-320, 375, Let-7a and 6073) were found to be more abundant in colon of MDE treatment mice compared with the untreated. Conclusion This study demonstrated that MDE have a therapeutic effect on colitis in vivo. Proving the effect of MDE on colitis will have implications for the potential of adding MDE as a therapeutic nutrient to be included in the formulas for IBD patients.


Cytotherapy ◽  
2020 ◽  
Vol 22 (5) ◽  
pp. S49-S50 ◽  
Author(s):  
Y. Geffen ◽  
R. Horev ◽  
N. Perets ◽  
E. Marom ◽  
U. Danon ◽  
...  

2021 ◽  
Vol 21 (2) ◽  
pp. 1085-1090
Author(s):  
Chunxia Zhang ◽  
Qian Qin ◽  
Hongle Li

Steroids are the main drugs currently used to treat asthma. However, the toxic and side effects of these drugs and the tolerance of the drugs due to long-term administration are still problems in the clinical treatment of asthma. Bavachinin has a good effect in the treatment of mouse asthma models, and it can effectively inhibit the expression of a variety of cytokines. However, it is extremely difficult to dissolve in water, has low bioavailability, and is quickly cleared in the blood. These characteristics limit its clinical application potential. In this study, nanotechnology was used to construct an effective oral drug delivery system. Through analysis of serum-related antibodies and cytokines, the system showed significant therapeutic effects on asthma-positive groups. Far-infrared imaging results showed that the system has a good targeted enrichment effect on pathological parts, while showing lower toxicity and higher therapeutic effect. Whether it is the splenocyte flow typing or the analysis of lung tissue, the system has verified the excellent treatment, and through the observation of paraffin sections of lung tissue, it was found that the bronchial morphology returned to normal after drug treatment, and the leakage of inflammatory cells was significantly reduced.


2014 ◽  
Vol 14 (12) ◽  
pp. 1048-1061 ◽  
Author(s):  
Fangming Kan ◽  
Guiping Ren ◽  
Mo Guo ◽  
Jianying Qi ◽  
Yu Zhang ◽  
...  

2015 ◽  
Vol 309 (8) ◽  
pp. L872-L878 ◽  
Author(s):  
Ikuo Murakami ◽  
Ran Zhang ◽  
Masayuki Kubo ◽  
Kenjiro Nagaoka ◽  
Eri Eguchi ◽  
...  

Allergic asthma caused by continuous allergen exposure evokes allergen-specific Th2 responses and is characterized by chronic airway inflammation and hyperresponsiveness. A previous report showed that rebamipide improved asthmatic symptoms in an ovalbumin/trypsin mice model. However, it is still unclear how rebamipide exerts its effects in asthma. In this study, rebamipide improved the asthmatic responses induced by mite exposure in NC/Nga mice, revealing the mechanism of this therapeutic effect. Rebamipide suppressed the infiltration of eosinophils into the airways and lung as well as attenuating the production of reactive oxygen species in tissues. In addition to these anti-inflammatory effects, rebamipide inhibited the production of IL-33, a member of the IL-1 family that drives the subsequent production of Th2-associated cytokines. These observations identify the point where rebamipide exerts its suppressive action on asthma and suggest that rebamipide has therapeutic potential in preventing mite-induced asthma.


2021 ◽  
Author(s):  
Xiaoying Zhang ◽  
Guodong Yang

Abstract Background: The aim of this study was to investigate the therapeutic effect and the underlying mechanism of resveratrol in high fat diet (HFD) and hyperlipidemia AP (HTG-AP) mice model. Methods: Following successful establishment of the HFD and HTG-AP mice model, resveratrol was administrated. 16sRNA sequencing of gut microbiota in colonic fecal, the LPS, MCP-1, TNF-α, and IL-6 expressions in serum, and MCP-1 expression of the pancreatic tissues were measured in HFD model. The MDA, SOD, T-AOC, TNF-α, and MCP-1 expressions; the NF‑κB proinflammatory signaling pathway‑related proteins in pancreatic tissues were determined. Histopathological examination was evaluated in both models.Results: Resveratrol effectively inhibited pancreatic pathological injury in both models. It reduced the MDA, SOD, T-AOC, TNF-α, and MCP-1 expressions and changed composition of gut microbiota in feces compared with the HFD model. Resveratrol also reduced oxidative stress by decreasing the level of MDA and increasing the levels of SOD and T-AOC. TNF-α and MCP-1 were decreased following the administration of resveratrol. Furthermore, resveratrol suppressed the NF‑κB proinflammatory signaling pathway in pancreatic tissues.Conclusions: The study suggested that resveratrol had therapeutic effect on HFD and HTG-AP mice model by regulating the gut microbiota, promoting antioxidant capacity and inhibiting proinflammatory cytokines via the NF‑κB inflammatory pathway. The results can provide evidence that resveratrol might be regarded as a promising therapeutic agent for HTG-AP.


2021 ◽  
Author(s):  
Haining Liu ◽  
Mingming Jin ◽  
Minxiu Ji ◽  
Wei Zhang ◽  
An Liu ◽  
...  

Abstract Background: Alzheimer’s disease (AD) is the most major dementia in the globe. Increasing evidence informs that exosomes from hypoxic pretreatment adipose-derived stem cells (ADSCs) could therapeutically affect cognitive function in AD-associated pathophysiology. However, their role and regulatory mechanism remain largely unknown. Methods: High-throughput sequencing was used to identify differentially expressed exosomal circRNAs from ADSCs or hypoxia pretreated ADSCs. Luciferase reporter assays and RT-qPCR were used to investigate the relationships between circ-Epc1, miR-770-3p, and TREM2. APP/PS1 double transgenic AD model mice were then utilized to study therapeutic effect regarding circ-Epc1 in ADSCs exosomes. BV2 cells were used to understand the regulatory relationship between circ-Epc1, miR-770-3p, and TREM2 and how these interactions modulated phenotypic transformation and inflammatory cytokine expression in microglia. Results: The result show that exosomes from hypoxia pretreatment ADSCs had a greater therapeutic effect at improving cognitive function by decreasing neuronal damage in the hippocampus. High-throughput sequencing found that circ-Epc1 played an important role in hypoxia pretreated ADSC exosomes regarding their ability to improve cognitive function. Luciferase reporter assays showed that TREM2 and miR-770-3p were downstream targets of circ-Epc1. Overexpressing miR-770-3p or downregulating TREM2 reversed the effects of circ-Epc1 on M2 microglia under LPS treatment. In vivo experiments showed that circ-Epc1-containing ADSC exosomes increased the therapeutic effect of exosome at improving cognitive function by decreasing neuronal damage and shifting hippocampal microglia from M1 to M2 polarization. Conclusions: Taken together, the data found that hypoxic pretreatment ADSCs exosomes improve cognition by delivery circ-Epc1 and shifting microglial M1/M2 polarization in alzheimer’s disease mice model.


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